The objective of this proposal is to develop an integrated microCT/microPET scanner for mouse imaging. Small animal imaging technologies are starting to play an important role in biomedical research, offering the opportunity to make repeated measurements of biological processes in intact laboratory animals in a completely non-invasive fashion. Combining molecular imaging (PET) with high resolution anatomic imaging (CT) offers advantages both in data interpretation and in data quantification compared with using either modality independently. Applications for this unique multi-modality device would include studies of tumor kinetics and metastasis in mouse models of human cancer, imaging of gene delivery and expression, and tracking of labeled cells in vivo. We propose to build an integrated system that incorporates amorphous selenium (a-Se) x-ray detector technology, a compact x-ray source and high resolution scintillation detectors in a co-planar geometry allowing CT and PET data to be acquired simultaneously. Preliminary studies have indicated the feasibility of this approach. In this proposal, detailed studies of x-ray spectra and the influence of filtration will determine appropriate x-ray tube settings/filters that produce the highest contrast to noise ratio for the lowest radiation dose. The a-Se detector will be characterized and compared with widely used phosphor/CCD based detector technology. The radiation dose to the mouse from the CT scan will be measured, and its biological effect, if any, investigated. The CT and PET detector components will be mounted into a gantry suitable for preliminary imaging studies in phantoms and in mice. The use of the CT data for correcting photon attenuation and for partial volume effects in the PET data will be investigated. Finally, the reproducibility of imaging anatomy and metabolism will be assessed both in repeat studies of the same subject, and in individual studies across subjects.